Electromagnetic radiation, including ultraviolet radiation, visible light, infrared radiation, radar, and radio waves, has been applied directly to tissue, particularly skin, for many purposes, including for treatment of dermatological conditions, resurfacing, and to combat the effects of aging. Electromagnetic radiation can be coherent in nature, such as laser radiation, or non-coherent in nature, such as flash lamp radiation. Coherent electromagnetic radiation can be produced by lasers, including gas lasers, dye lasers, metal-vapor lasers, and/or solid-state lasers. Depending on the type of electromagnetic radiation (laser, flash lamp, radio frequency, etc.), the mode of usage (continuous wave or pulsed), and other parameters, such as the pulse width, the energy density and the power, different types of treatments and effects can be accomplished.
Electromagnetic radiation has been used to treat common dermatological problems, including hypervascular lesions, pigmented lesions, acne scars, rosacea, and hair removal. Electromagnetic radiation has also been used in aesthetic surgery to achieve better cosmetic appearances by resurfacing the skin and remodeling the different layers of skin, improving the appearance of wrinkled or aged skin. Generally, skin resurfacing is understood to be the process by which the top layers of the skin are completely removed using chemicals, mechanical abrasion or electromagnetic radiation to promote the development of new, more youthful looking skin and stimulate the generation and growth of new skin. For example, pulsed CO2 laser skin resurfacing typically ablates the existing tissue to a layer below the papillary dermis, which can cause heat-induced coagulation to several hundred micrometers below the original skin surface. Following resurfacing, the tissue is regenerated and remodeled, producing skin with a better cosmetic appearance (i.e., improving photodamage, the appearance of wrinkles, acne scars, and other unwanted features).
A number of possible mechanisms may be responsible for the improvement of the appearance of the skin following resurfacing. Ablation and subsequent regeneration and remodeling of collagen through heat-induced collagen contraction may be involved. For example, in laser skin remodeling, the laser energy penetrates into the deeper layers of the skin and is aimed at altering and stimulating regeneration of the structure of extra-cellular matrix materials, such as collagen, that contribute to the youthful appearance of skin. Another possible mechanism which may lead to improvement in the appearance of skin is tightening of the skin through wound contraction which occurs as part of the normal wound healing process. Some studies have concluded that heat-induced collagen tightening is responsible for the long-lasting skin tightening produced by CO2 laser skin resurfacing. (See, e.g., Fitzpatrick R E et al. (2000) Collagen Tightening induced by carbon dioxide laser versus erbium:YAG laser, Lasers Surg Med, 27(5):395-403).
Generally, the desired effects on the skin are thought to be accomplished by electromagnetic radiation-induced heating of the tissue. Induced heating for specific temperature and heating time combinations can result in thermal coagulation, cell necrosis, hemostasis, melting, welding, ablation and/or gross alteration of the extra-cellular matrix. When using electromagnetic radiation for skin resurfacing and/or remodeling, an important objective has been to provide uniform treatment across the desired treatment site. With such treatments, particular care is exercised, either by the physician alone or by combining the physician's judgment with intelligence that is built into the dermatological system, to leave no tissue untreated in the targeted region of the skin. Whether using a broadly radiating pulsed beam of radiation or a focused beam of radiation that produces a relatively smaller spot size, the goal has been to expose the entire treatment area to the electromagnetic radiation, in order to heat the entire volume of tissue in the treatment area and bring about the desired change. It has been widely reported that such broad area or bulk treatments result in undesirable side effects such as intolerable pain, prolonged erythema, swelling, occasional scarring, extended healing times, and infection.
Various forms of electromagnetic radiation, including laser radiation and radio frequency (RF) radiation, are increasingly being used for skin rejuvenation, including tightening the skin, particularly the skin of the facial area, to reduce the appearance of wrinkles and combat the effects of aging. Radiation sources frequently used for skin rejuvenation include CO2 lasers, short pulsed Erbium:Ytrrium-Aluminum-Garnet (Er:YAG) lasers, combined CO2/Er:YAG lasers, variable pulsed Er:YAG lasers, ablative radiofrequency devices, non-ablative lasers, and intense light sources. Of the commonly used treatments, resurfacing treatments using CO2 lasers are generally considered to provide the most effective treatment for wrinkles and photoaging, as they produce the greatest degree of tightening of skin. (See, e.g., Goldberg D J, (2003) Lasers for facial rejuvenation, Am J Clin Dermatol 4(4):225-34). However, these bulk CO2 laser treatments ablate large areas of the skin, cause dermal wounds, produce significant thermal effects within the treated tissue, and require long periods of time to heal—in many cases, up to a two week period of second-degree burn wound management and months of prolonged erythema.
Less aggressive treatments, such as lower energy or non-ablative lasers, while still effective in rejuvenating skin, typically produce fewer and less severe side effects and heal more rapidly. However, these less aggressive treatments typically do not produce as great of long-term improvements in tightening of skin and reduction in the cosmetic appearance of wrinkles as bulk CO2 laser treatments. An objective of non-ablative skin rejuvenation is to induce a thermal wound repair response in the papillary and upper reticular layers of the dermis (approximately 100-400 micrometers below the surface of the skin) while sparing at least some cells at the junction between the dermal and epidermal layers of the skin. One approach used to achieve this objective is to spare the epidermal layer. To spare the epidermal layer, low fluences (laser energy densities) can be used. Unfortunately, such low levels are generally inadequate to promote the kinds of stimulation that is required to produce the desired tightening of the skin and reduction in the appearance of wrinkles. Thus, nonablative approaches can result in minimal efficacy. In most cases, minimal dermal matrix remodeling and minimal clinical responses (e.g., wrinkle reduction, retexturing, dyschromia reduction, and telangiectasia removal) are achieved by these procedures (See, e.g., Nelson et al, (2002) What is Nonablative Photorejuvenation of Human Skin, Seminars in Cutaneous Medicine and Surgery, 21:(4)238-250, 2002; Leffell D (2002) Clinical Efficacy of Devices of Nonablative Photorejuvenation, Arch. Dermatol. 138:1503-1508). Therefore, there is an unmet need for methods and devices which provide electromagnetic radiation treatments which spare the epidermal layer of the skin, but achieve enough stimulation of dermal matrix remodeling to be clinically effective in rejuvenating skin, tightening skin and treating wrinkles.
Various devices and approaches have been proposed to reduce the extent and duration of the side effects produced by treating tissue with electromagnetic radiation. One approach to minimize the effects of bulk heating of the skin is to cool the skin before, during or immediately following treatment, in an effort to reduce the level of thermal damage to the epithelium. While methods and systems such as these can reduce the damage to the skin during treatment, cooling systems pose practical limitations because of their added complexity. Another approach to sparing the epithelium includes systems that deliver electromagnetic radiation over a relatively large tissue surface area with the radiation focused in the dermis. Treatment methods such as these are designed to cover the target tissue in the plane of the skin completely with overlapping treatment zones so that no tissue in the treated portion of skin is left unexposed to electromagnetic radiation. However, by their nature, bulk treatment methods lead to an increase in clinical side effects and to an increase in healing time, and force physicians to lower the treatment intensity, resulting in less effective treatments.
When electromagnetic radiation at an effective treatment level is applied to tissue or skin, a burn or an acute wound is usually created. For acute wounds, the skin heals by three distinct ‘response to injury’ waves. The initial inflammatory phase has a duration lasting minutes to days, and seamlessly transitions into the cell proliferative phase, lasting 1 to 14 days. This cell proliferative phase is slowly replaced by the dermal maturation phase that lasts from weeks to months (See, e.g., Clark R (1999) Mechanisms of cutaneous wound repair. In: Fitzpatrick T B, ed. Dermatology in General Medicine, 5th Ed., McGraw-Hill, New York, N.Y. pp. 327-41).
In general, a direct correlation exists between the size of the injury and the time required for complete repair. However, the inflammatory phase is a function of cellular necrosis, particularly epidermal (i.e., keratinocyte) necrosis, and a direct correlation exists between cellular necrosis and the inflammatory phase. Increased cellular necrosis, particularly epidermal necrosis, prolongs the inflammatory phase. Prolonging and/or accentuating the inflammatory phase may be undesirable from a clinical perspective due to increased pain and extended wound repair, and may retard subsequent phases of wound repair. The cause(s) of this prolonged inflammatory phase are not well understood. However, injuries caused by electromagnetic radiation are associated with early and high levels of dermal wound repair (e.g., angiogenesis, fibroblast proliferation and matrix metalloproteinase (MMP) expression) but delayed epidermal resurfacing (See, e.g., Schaffer et al, (1997) Comparisons of Wound Healing Among Excisional, Laser Created and Standard Thermal Burn in Porcine Wounds of Equal Depth, Wound Rep Reg 5(1):51-61). Unfortunately, most of the skin resurfacing efforts and selective photothermolysis treatments that affect large contiguous areas of chromophores result in a prolonged, exaggerated inflammatory phase leading to undesirable consequences such as delayed wound repair. The prolonged inflammatory phase also leads to the pain experienced by most patients undergoing skin resurfacing procedures. Undesirable extended inflammatory response phase can be attributed to the bulk heating of the skin with little or no healthy tissue, particularly keratinocytes, left behind in the area where the skin was exposed to the electromagnetic radiation. Particularly when uniform treatment is desired and the entire target tissue volume is exposed to electromagnetic radiation without sparing any tissue within the target volume, pain, swelling, fluid loss, prolonged reepitheliazation and other side effects of dermatological laser treatments are commonly experienced by patients.
Increasingly, conventional bulk skin treatment methods are being replaced by various fractional treatment methods, as the use of fractional treatment methods has been found to produce fewer and less severe side effects than conventional bulk treatment methods, including reduced damage to the epidermal layers of the skin. Fractional treatment methods involve the generation of a large number of treatment zones within a region of tissue. The electromagnetic radiation impacts directly on only the relatively small treatment zones, instead of impacting directly on the entire region of tissue undergoing treatment, as it does in conventional bulk treatments. Thus, a region of skin treated using a fractional electromagnetic radiation treatment method is composed of a number of treatment zones where the tissue has been altered by the radiation, contained within a larger volume of tissue that has not been altered by the radiation. Fractional treatment methods make it possible to leave substantial volumes of tissue unaltered and/or viable within a treatment region.
Various fractional treatment methods have been used for treating both existing medical (e.g., dermatological) disease conditions and for improving the appearance of tissue (e.g., skin) by intentionally generating regions of thermally altered tissue surrounded by unaltered tissue. Fractional treatment methods generally offer numerous advantages over existing approaches in terms of safety and efficacy. Fractional treatment methods can reduce the undesirable side effects of pain, erythema, swelling, fluid loss, prolonged reepithelialization, infection, and blistering generally associated with laser skin resurfacing. By sparing healthy tissue around the thermally altered tissue, fractional treatment methods can increase the rate of recovery of the treatment zones by stimulating skin remodeling and wound repair mechanisms. Fractional treatment methods can also reduce or eliminate the side effects of repeated electromagnetic radiation treatments to tissue by controlling the extent of tissue necrosis due to exposure to electromagnetic radiation.
Among other approaches, U.S. Pat. No. 6,997,923 describes methods of treating a volume of a patient's skin by irradiating portions of the volume. The patent describes a method for performing a treatment on a volume located at area and depth coordinates of a patient's skin, the method involving providing a radiation source and applying radiation from the source to an optical system which concentrates the radiation to at least one depth within the area coordinates of the volume, the at least one depth and the selected areas defining three-dimensional treatment portions of the volume within untreated portions of the volume. The method is described as producing irradiated portions of tissue or treatment regions, where each irradiated portion is surrounded by a non-irradiated portion, and each treatment region is separated from other treatment regions by untreated tissue.
U.S. patent application Ser. No. 10/888,356 (US Patent Application Publication Number US 2005/049582) describes methods and apparatus for generating isolated, non-contiguous tissue volumes having treatment zones comprising necrotic tissue, surrounded by zones of viable tissue that are capable of promoting healing of the target tissue. Specifically, the application describes creating a plurality of microscopic treatment zones in a predetermined treatment pattern, wherein a subset of the plurality of discrete microscopic treatment zones includes discrete microscopic treatment zones comprising necrotic tissue volumes having an aspect ratio of at least about 1:2.
U.S. patent application Ser. No. 11/097,825 (US Patent Application Publication Number US 2005/0222555) describes apparatus and methods for treating skin by providing a skin damaging means and applying the skin damaging means to create a plurality of micro-lines of damaged tissue in a region of skin separated by regions of undamaged skin tissue, wherein the micro-lines are substantially parallel and traverse at least part of said region of skin being treated. The application defines ‘micro-lines’ as narrow regions of damaged dermal tissue, generally less than 1 mm in width, that extend from the surface of the skin into the epidermis and, optionally, through the epidermis and into the dermal layer. The micro-lines are long in one direction along the surface of the skin, generally at least four to five times as long as the width of the micro-lines, and may traverse part or all of the region of skin being treated.
U.S. patent application Ser. No. 11/098,036 (US Patent Application Publication Number US 2006/0004347) describes devices, systems and methods of treatment of tissue with electromagnetic radiation (EMR) to produce lattices of EMR-treated islets in the tissue. The islets are described as being separated from each other by non-treated tissue (or differently- or less-treated tissue), and numerous advantages are attributed to the production of lattices of EMR-treated islets in the tissue rather than large, continuous regions of EMR-treated tissue.
These treatment methods can be suitable for treating skin to achieve a better cosmetic surface by resurfacing the skin and remodeling the layers of skin to improve the appearance of wrinkled or aged skin while avoiding extensive damage to the epithelial layer of the skin. Using these treatment methods can produce small to moderate increases in tightening of the skin and the cosmetic appearance of wrinkles due to shrinkage of collagen fibrils subjected to elevated temperature or coagulation of localized areas in the dermis and hypodermis. However, the level of improvement in skin tightening and the appearance of wrinkles achieved using these treatment methods appears to be less than the level of improvement achieved using bulk ablative treatments, such as conventional pulsed CO2 laser skin resurfacing. A need remains in the art for methods of treatment and devices which provide the benefits of fractional electromagnetic radiation treatment methods while achieving significant increases in skin tightening and the appearance of wrinkles more comparable to those produced by bulk electromagnetic radiation treatment methods and devices.